This is a proposal to continue our studies of basic mechanism of seizures. This application describes a re-organized program project consisting of three component research projects and a support autoradiography core project which are closely inter-related and have a common overall goal to characterize functional anatomy normal and epileptic brain. The major objectives of the component projects are 1) to define the role(s) of the mammillary bodies and their connections in brain in pathophysiologic processes responsible for initiation, propogation and/or termination of generalized seizures; 2) to determine how experimental focal sensorimotor seizures travel through local and long circuits in brain causing an increase in excitability over time; and 3) to physiologically characterize sensory, motor, associative and language cortex in human brain for the purpose of improving surgical treatment of epilepsy, to develop more comprehensive methods for localizing seizure foci in human brain, and to determine the effect of surgical treatment of epilepsy on regional metabolic abnormalities associated with seizure foci. The autoradiography core will maintain and develop quantitative image analysis techniques for autoradiographic experiments and develop new radioactive tracers, mathematical models and quantitative autoradiographic methods for studying seizures. The program brings together several excellent and productive basic and clinical scientists with skills and interests in the fields of anatomy, biochemistry, physiology, pharmacology, radiology, neurology and neurological surgery. Our research should provide greatly improved understanding of normal brain and pathophysiological mechanisms of both experimental and clinical seizures. This information will eventually improve diagnosis and treatment of the patient with epilepsy.